CDKN1B (p27/kip1) enhances drug-tolerant persister CTCs by restricting polyploidy following mitotic inhibitors.

ABSTRACT: The mitotic inhibitor docetaxel (DTX) is often used to treat endocrine-refractory metastatic breast cancer, but initial responses are mitigated as patients develop disease progression. Using a cohort of ex vivo cultured circulating tumor cells (CTCs) from patients with heavily pretreated breast cancer (n=18), we find distinct patterns of response to DTX, which are intrinsic and independent of past clinical treatment with taxanes. In some CTC cultures, treatment with a single dose of DTX results in complete cell killing, associated with accumulation of nonviable polyploid (≥8 N) cells arising from endomitosis. In other CTC cultures, a transient viable drug-tolerant persister (DTP) population emerges, ultimately enabling renewed proliferation of CTCs with preserved parental cell ploidy and r

SUBMITTER: Horwitz E 

PROVIDER: S-EPMC12280942 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature